仿生活性人工骨诱导兔椎板间多节段脊柱融合的研究  

Experimental posterior interlaminar spinal fusion in rabbits with a new biomimetic grafting material

作　　者：马兴[1] 胡蕴玉[1] 熊卓[2] 颜永年[2] 吕荣[1] 王军[1] 李丹[1] 徐新智[1] 白建萍[1] 

机构地区：[1]第四军医大学附属西京医院全军骨科研究所,西安710032 [2]清华大学机械系激光快速成形制造中心

出　　处：《中华创伤杂志》2005年第7期491-495,共5页Chinese Journal of Trauma

基　　金：军队"十五"重点课题基金资助项目(01Z079);国家博士后科学基金资助项目(2003033523)

摘　　要：目的探讨采用先进快速成形(rapidprototyping,RP)制造技术结合骨组织工程方法研制新型仿生活性人工骨,系统研究该人工骨在兔腰椎椎板间多节段脊柱融合的情况。方法首先应用RP技术制备粒度均匀的颗粒型聚乳酸-聚羟乙酸/磷酸三钙[Poly(DL-lactic-co-glycolicacid)/Tricalciumphosphate,PLGA/TCP]复合人工骨载体材料,进一步将该载体材料与天然提取牛骨形态发生蛋白(bovinebonemorphogeneticprotein,bBMP)高效复合制备仿生活性人工骨,扫描电镜观察RP制备的载体材料及人工骨超微结构。雄性新西兰兔42只,均于L2～4左侧椎板及椎小关节表面分别植入颗粒型PLGA/TCP人工载体材料(A组)、颗粒型仿生活性人工骨(B组)和自体髂骨颗粒(C组),每组14只,于术后4,8和12周定期拍摄脊柱X线片,并于以上时相点按时取材(每组各取材2,2和10只兔),大体观察、手法检测及组织学方法(HE染色、三色光镜观察及四环素-钙黄绿素荧光检测)系统评价脊柱融合情况。结果先进RP制备的PLGA/TCP复合人工骨载体具有规则的空间网状支架结构、相互贯通的孔隙及材料表面微孔特征,均有利于bBMP的高效均匀复合。术后所有实验动物均存活,A组单纯载体材料植入后逐渐降解,但无骨诱导活性及新骨形成能力。B组仿生活性人工骨植入具有强的诱骨活性及骨性融合能力,不仅成骨早、新骨形成量大,而且在新骨形成及改塑的同时载体材料逐渐降解完全,术后12周可形成较为典型的骨小梁及骨髓结构,成骨代谢活性亦接近正常,所形成融合块较大、强度高。C组自体髂骨移植能达到良好的骨性融合,但至术后12周其所形成的新骨结构与B组相比,尚需进一步塑形及完善,所形成的融合块较小。术后12周,三组多节段(L2,3、L3,4)脊柱融合率分别为0%(0/20)、90%(18/20)和55%(11/20),B组融合率显著高于C组(P<0.05),C组融合率显著高于A组(P<0.01)。结论先进RP技�Objective To investigate the effectiveness of rapid prototyping (RP) technique manufactured Poly (DL-lactic-co-glycolic acid)/Tricalcium phosphate (PLGA/TCP) loaded with bovine morphogenetic protein (bBMP)as a new graft material for spinal fusion in an animal model. Methods Firstly, three-dimensional PLGA/TCP granular scaffolds were synthesized by RP and bBMP was loaded into the granular scaffolds. Secondly, both PLGA/TCP scaffolds and PLGA/TCP-bBMP composites were observed by scanning electron microscopy. Thirdly, 42 healthy New Zealand white rabbits weighing 2-2.5 kg (four months old) unilaterally underwent posterior interlaminar spine fusion at the L_ 2~4 level (on the left side) using one of the following graft materials: RP synthesized PLGA/TCP granules (Group A, 14 rabbits), PLGA/TCP-bBMP composites (Group B, 14 rabbits) and autogenous iliac bone graft (Group C, 14 rabbits). The animals in each group were killed at the end of 4th week (two animals), 8th week (two animals) and 12th week (10 animals) after surgery. The spine fusion was evaluated by a general observation, a manual palpation test, histological analyses and radiography. Results RP technique established PLGA/TCP scaffolds with good biomaterial properties including satisfactory microstructure and porosities. bBMP was efficiently loaded into the granular scaffolds to produce a new biomimetic artificial grafting material. In Group A, histological analyses revealed that PLGA/TCP scaffolds were biocompatible and biodegradable. Whereas, no newly formed bone was found within and in contact with the implanted granules. In Group B, highly cellular bone marrow between the newly formed trabecular bone were present in the fusion mass. In Group C, there was a reduced amount of newly formed bone at 12th week compared with Group B. Twelve weeks after surgery, the fusion rate of posterior interlaminar arthrodesis (at L_ 2,3 and L_ 3,4 ) in Group A, B and C was 0% (0/20), 90% (18/20) and 55% (11/20), respectively. The fusion rate in Group B was significantly high

关 键 词：脊柱融合 生活性 多节段 牛骨形态发生蛋白 自体髂骨移植 protein 载体材料 复合人工骨 组织工程方法 PLGA 扫描电镜观察 构建组织工程 RP技术 超微结构 BBMP 骨性融合 新骨形成 组织学方法 骨诱导活性 人工骨植入 骨移植材料 

分 类 号：R687.3[医药卫生—骨科学]